The current standard of care for chronic HCV genotype (GT) 1 infection is telaprevir or boceprevir + peginterferon/ribavirin. Patients with IL28B CT or TT genotypes, prior null response to pegIFN-alfa/RBV, or <1 log decline in HCV RNA after 4-week pegIFN-alfa/RBV therapy have high rates of virologic failure during or after standard of care therapy.

In a Phase 2, randomized, open-label, parallel-group study, Mark Sulkowski, MD, from John Hopkins University School of Medicine, Baltimore, MD, and colleagues assessed the safety and efficacy of DCV + SOF with or without RBV for 24 weeks in a total of 41 genotype (GT) 1 non-cirrhotic patients with previous breakthrough (n=15), relapse (n=13), or non-response (n=14) to peginterferon/ribavirin + telaprevir (n=33) or boceprevir (n=9).

At Week 4, HCV RNA <25 IU/mL was achieved in 21/21 (100%) of the DCV + SOF group and in 19/20 (95%) of the DCV + SOF + RBV group. All patients achieved HCV RNA <25 IU/mL by the end of treatment. No patients experienced breakthrough or relapse, and all patients with available data achieved SVR12.

Overall, SVR12 was achieved in 98% of non-cirrhotic GT1 patients with prior TVR or BOC with the once-daily DCV + SOF combination with or without RBV for 24 weeks.

Adverse events occurring in ≥10% of patients in this study were fatigue, headache, alopecia, arthralgia, constipation, and diarrhea. All events were mild or moderate (Grade 1/2).

Dr. Sulkowski stated, “The combination of two potent direct-acting antivirals with different viral targets is effective in patients who failed peginterferon/RBV and a protease inhibitor.” Currently multiple Phase 2 and 3 trials assessing the efficacy and safety of different daclatasvir-based regimens are ongoing.